• Title/Summary/Keyword: PD 제도

Search Result 222, Processing Time 0.038 seconds

Drug Interaction between Ginseng Extract (GE) and Sorafenib (쏘라페닙과 홍삼추출물간의 약물상호작용)

  • Lee, Nam-Hee;Park, Ho-Jae;Rho, Ja-Sung;Kim, Mi-Kyung;Lee, Yu-Kyoung;Cho, Eun-A;Heo, Jeong;Cho, Mong;Hwang, Tae-Ho
    • Journal of Life Science
    • /
    • v.21 no.11
    • /
    • pp.1518-1525
    • /
    • 2011
  • Sorafenib is the only approved systemic, therapeutic agent for hepatocellular carcinoma (HCC). The use of Ginseng Extract (GE) in cancer patients is growing worldwide; however, drug interaction between sorafenib and GE has not been illuminated. Four different human cancer cell lines including HepG2 were used and immunocompetent mice were implanted subcutaneously with a mouse HCC cell line. Treatment with low dose GE stimulated cell growth, while a high dose inhibited growth. pERK (phosphorylation of extracellular signal-regulated kinase) was concomitantly increased and decreased respective of different doses of GE. Antitumoral effect of sorafenib decreased in non-proliferating phase cells but was sensitized after low dose GE (LDG) treatment. PD98059 (ERK phosphorylation inhibitor) efficiently blocked ERK phosphorylation, resulting in loss of sorafenib sensitization even after LDG treatment. In the HCC mouse model, LDG alone slightly increased tumor size while sorafenib alone significantly decreased it. However, a combination of LDG and sorafenib significantly decreased tumor size compared with sorafenib alone. Increase of pERK was observed in some normal mice organs and mild inflammatory change was observed in some of these organs, suggesting pERK activation by LDG may cause unexpected toxicity in normal cells. GE, dose-dependently, induced stimulation or inhibition in some human cancer cell lines. Combinational use of GE and sorafenib possibly potentiated an antitumoral response to sorafenib. pERK level has been provided as a potential predictive marker for sorafenib. Our result may suggest GE's dual effects in relation to pERK level in HCC cancer cell lines, and that certain doses of GE can sensitize sorafenib.

The Protective Effect of Inhaled Heparin, Cromolyn, Budesonide, and Furosemide on Exercise-induced Asthma (운동유발성 천식의 기관지 수축에 대한 Heparin, Cromolyn, Budesonide, Furosemide 흡입 치료의 효과)

  • Lee, Sin-Hyung;Shim, Jae-Jeong;Lee, Sang-Youb;Cho, Jae-Youn;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
    • /
    • v.45 no.6
    • /
    • pp.1188-1198
    • /
    • 1998
  • Background : The purpose of the present study was to determine the protective effect of antiasthmatic activity of inhaled heparin, cromolyn sodium, budesonide, furosemide in exercise-induced asthma(EIA). The other important considerable point of this study was the mechanism of bronchoconstriction on EIA. Methods : Eight subjects with a history of EIA were studied on 5 different experiment days. After obtaining baseline FEV1 and FVC, subjects performed a standardized exercise challenge. EIA was assessed by measurement of FEV1 before and after exercise. On experiment day 4, the exercise challenge was performed after the subjects inhaled either heparin (1,000 units/kg/day for 5 days), furosemide (1mg/kg for 5 days), cromolyn (4mg/day for 5 days), or budesonide (400μg/day for 5 days). On experiment day 5, the methacholine bronchial provocation test was performed. On experiment day 3, activated partial thromboplastine time(aPTI) was checked. Results : Maximum decrements of FEV1 (mean±SE) among 0 to 120 minutes after exercise were as follows : heparin was 83.1±4.81 (p=0.010), furosemide was 80.5±6.87 (p=0.071), cromolyn was 86.8±6.53 (p=0.340), and budesonide was 79.4±7.31 (p=0.095). Above medications were compared to the control value (72.5±18.2) by paired t-test. No medications had effect on PD20 of methacholine bronchial provocation test The results were control 1.58±0.49μmol), heparin (4.17±1.96μmol), furosemide (1.85±0.86μmol), cromolyn (2.19±0.89μmol), and budesonide (3.38±1.77μmol), respectively(p>0.05). The inhaled heparin had no effect of anticoagulation. Conclusion : These data demonstrate that inhaled heparin has a protective effect on EIA. The effect of inhaled cromolyn was statistically absent with manufacture's recommended dosage on EIA. So, the dosage of cromolyn should be carefully evaluated in future. Although inhalation of budesonide and furosemide have no statistical significance compared to control, these drugs also have some protective effects on EIA.

  • PDF

Insulin-Like Growth Factor-I Induces Androgen Receptor Coactivator Expression in Skeletal Muscle Cells through the p38 MAPK and ERK1/2 Pathways (C2C12 세포에서 insulin-like growth factor-I이 p38 MAPK, ERK1/2 신호전달 경로를 통해 엔드로젠 수용체 coactivator 발현에 미치는 영향)

  • Park, Chan-Ho;Kim, Hye-Jin;Kim, Tae-Un;Lee, Won-Jun
    • Journal of Life Science
    • /
    • v.21 no.2
    • /
    • pp.242-250
    • /
    • 2011
  • Although insulin-like growth factor-I (IGF-I) and androgen receptor (AR) coactivators are well known effectors of skeletal muscle, the molecular mechanism by which signaling pathways integrating AR coactivators and IGF-I in skeletal muscle cells has not been previously examined. In this study, the effects of IGF-I treatment on the gene expression of AR coactivators in the absence of AR ligands and the roles of the p38 MAPK and ERK1/2 signaling pathways in IGF-I-induced AR coactivators induction were examined. C2C12 cells were treated with 250 ng/ml of IGF-I in the presence or absence of specific inhibitors p38 MAPK (SB203580) or ERK1/2 (PD98059). Treatment of C2C12 cells with IGF-I resulted in increased in GRIP-1, SRC-1, and ARA70 protein expression. The levels of GRIP-1, SRC-1, and ARA70 mRNA were also significantly increased after 5min of IGF-I treatment. IGF-I-induced AR coactivator proteins were significantly blocked by pharmacological inhibitors of p38 MAPK and ERK1/2 pathways. However, there was no significant effect of those inhibitors on IGF-I-induced mRNA level of AR coactivators, suggesting that AR coactivators are post-transcriptionally regulated by IGF-I. Furthermore, the present results suggest that IGF-I stimulates the expression of AR coactivators by cooperative activation of the p38 MAPK and ERK1/2 pathways in C2C12 mouse skeletal muscle cells.

The Korean Girl Group Kara's Differentiation Strategy Which Overcome the Trilemma and Led to the Great Reversal Success (삼중고 탈피 후 대역전의 성공을 이끈 걸 그룹'카라'의 차별화 전략)

  • Kim, Jeong-Seob
    • Journal of Korea Entertainment Industry Association
    • /
    • v.15 no.2
    • /
    • pp.169-178
    • /
    • 2021
  • The Korean girl group "Kara" has suffered the trilemma of its de facto failure to debut, the crisis of team breakup, and the CEO crisis of the agency. But the group has made an outstanding achievement in the history of Korean pop music after overcoming all odds. Their success strategy has never been disclosed by insiders involved in Kara's total music projects. This study has been carried out in the analysis of the strategy to provide academic implications and to honor the contribution of the late CEO Ho-yeon Lee and Kara's key member Ha-ra Gu. Therefore, between Nov. and Dec. 2020, we conducted in-depth interviews with managers, composers, stylists and Ha-ra Gu(Only in 2019, before her death) who took part in the project. The research model is set up by combining Porter's Competitive Advantage Strategy and the music value chain model into categories of "Product Innovation Differentiation (PD)" (producing, album production, performance activities) and "Marketing Differentiation (MD)" (market targeting, image specialization, promotion and communication). The analysis showed that the PD focused on complete rediscovered harmonization and revalued members' personality and sincerity with peppy songs and dainty dances as well as emission of "bright energy" which caused healing effects instead of mimicking other star singers recklessly. In terms of MD, they selected Japan's 10-20s as their main market, increasing intimacy with fans and media with the image of cute+pretty+classy+sexy. The result suggests that Poter's differentiation can function as a meaningful strategy frame in the fostering, hit, and revival of idol groups. In addition, it reaffirmed that spontaneous and passionate activities of early-stage or celebrity fan may serve as a valid catalyst for realizing differentiation, as Kara's caller of Japanese actor Gekidan Hitori caused a strong "priming effect" that drove Kara's unexpected wonderful success in Japan.

In Vitro Properties and Biodistribution of Tc-99m and Re-188 Labeled Monoclonal Antibody CEA79.4 (Re-188과 Tc-99m 표지 단일클론항체 CEA79.4의 생체외 특성과 생체내 분포)

  • Hong, Mee-Kyoung;Jeong, Jae-Min;Yeo, Jeong-Seok;Kim, Kyung-Min;Chang, Young-Soo;Lee, Yong-Jin;Lee, Dong-Soo;Chung, June-Key;Lee, Myung-Chul;Lee, Seung-Jin
    • The Korean Journal of Nuclear Medicine
    • /
    • v.32 no.6
    • /
    • pp.516-524
    • /
    • 1998
  • Purpose: Radiolabeled CEA79.4 antibody has a possibility to be used in radioimmunoscintigraphy or radioimmunotherapy of cancer. We investigated the in vitro properties and biodistribution of CEA79.4 antibody labeled with Re-188 or Tc-99m. Materials and Methods: CEA79.4 was reduced by 2-mercaptoethanol to produce-SH residue, and was labeled with Re-188 or Tc-99m. For direct labeling of Tc-99m, methylene-diphosphonate was used as transchelating agent. CEA79.4 in 50 mM Acetate Buffered Saline (ABS, pH 5.3) was labeled with Re-188, using stannous tartrate as reducing agent. In order to measure immunoreactivity and the affinity constant of radiolabeled antibody, cell binding assay and Scatchard analysis using human colon cancer cells SNU-C4, were performed. Biodistribution study of labeled CEA79.4 was carried out at 1, 14 and 24 hr in ICR mice. Results: Labeling efficiencies of Tc-99m and Re-188 labeled antibodies were 92.4±5.9 and 84.7±4.6, respectively, In vitro stability of Tc-99m-CEA79.4 in human serum was higher than Re-188-CEA79.4. Immunoreactivity and affinity constant of Tc-99m-CEA79.4 were 59.2% and 6.59×109M1, respectively, while those of Re-188-CEA79.4 were 41.6% and 4.2×109M1, respectively. After 24 hr of administrations of Re-188 and Tc-99m labeled antibody, the remaining antibodies in blood were 6.32 and 9.35% ID/g respectively. The biodistribution of each labeled antibody in other organs was similar because they did not accumulate in non-targeted organs. Conclusion: In vitro properties and biodistribution of Re-188-CEA79.4 were similar to those of Tc-99m-CEA79.4. It appears that Re-188-CEA79.4 can be used as a suitable agent for radioimmunotheraphy.

  • PDF

Protective Effect of Rehmanniae Radix Preparata Extract on H2O2-induced Apoptosis of ECV304 Cells (숙지황(熟地黃) 추출물이 H2O2에 의해 유도된 ECV304 세포의 apoptosis에 미치는 영향)

  • Kim, In-Gyu;Ju, Sung-Min;Park, Jin-Mo;Jeon, Byung-Jae;Yang, Hyun-Mo;Kim, Won-Sin;Jeon, Byung-Hun
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.23 no.1
    • /
    • pp.76-83
    • /
    • 2009
  • Rehmannia Radix Preparata (RRP) used to nourish Eum and enrich blood for consumptive fever, aching, and limpness of the loins and knees, and to replenish essence for tinnitus, premature greying of beard and hair. In the present study, we studied about the protective effect of RRP on hydrogen peroxide-induced oxidative stress in human vascular endothelial cells. ECV304 cells were preincubated with RRP (100, 200, 300 and 400μg/m) for 12hr and then treated with 600μM H2O2 for 12hr. The protective effects of RRP on H2O2-induced apoptosis in ECV304 cells was determined by using MTT assay, FDA-PI staining, flow cytometric analysis, caspase-3 activity assay, ROS assay and western blot. The results of this experiment showed that RRP inhibited H2O2-induced apoptosis and ROS production in ECV304 cells. Moreover, RRP increased ERK activation that decreased in H2O2-treated ECV304 cells, and inhibited p38 and JNK activation. Furthermore, RRP increased expression of heme oxygenase-1 (HO-1) in H2O2-treated ECV304 cells. Also, HO-1 protein expression induced by RRP was reduced by the addition of ERK inhibitor (PD98059) in H2O2-treated ECV304 cells. These results suggest that protective effect of RRP on H2O2-induced oxidative stress in ECV304 cells may be associated with increase of ERK activation and HO-1 protein, and reduction of p38 and JNK activation.

CCNU, Vinblastine and Prednisone Treatment for Grade II Dermal Mast Cell Tumor in a Yorkshire terrier dog (CCNU, Vinblastine과 Prednisone으로 병용 치료한 요크셔 테리어 개의 Grade II 피부 비만세포종 증례)

  • Seo, Kyoung-Won;Lee, Jong-Bok;Kim, Seoung-Soo;Bhang, Dong-Ha;Jung, Jin-Young;Hwang, Cheol-Yong;Kim, Dae-Yong;Youn, Hwa-Young;Lee, Chang-Woo
    • Journal of Veterinary Clinics
    • /
    • v.24 no.4
    • /
    • pp.618-621
    • /
    • 2007
  • An 11-year-old, castrated male Yorkshire terrier dog was presented with multiple plaques on right inguinal region. Grade II mast cell tumor was diagnosed. The dog was treated with Vinblastine and prednisone(PDS) initially. Because of poor response of the dog, CCNU was added for more aggressive treatment. After 5 weeks treatment of with CCNU, vinblastine and PDS, the lesion was improved. Moderate leukopenia was shown after 4 cycles of chemotherapy. The chemotherapy was re-administered since the patient recovered from the leukopenia. Though the same protocol was applied, no improvement of the lesion was observed. Moreover, the general body condition of the dog became worse and was euthanized by the owner's request. Necropsy was not permitted. The survival time was 330 days after start of the chemotherapy.

Effects of Achyranthoside C Dimethyl Ester on Heme Oxygenase-1 Expression and NO Production (Heme Oxygenase-1 발현과 NO 생성에 미치는 Achyranthoside C Dimethyl Ester의 효과)

  • Bang, Soo Young;Song, Ji Su;Moon, Hyung-In;Kim, YoungHee
    • Journal of Life Science
    • /
    • v.25 no.9
    • /
    • pp.976-983
    • /
    • 2015
  • Achyranthoside C dimethyl ester (ACDE) is an oleanolic acid glycoside from Achyranthes japonica which has been used in traditional medicine for the treatment of edema and arthritis. In this study, we investigated the anti-inflammatory effects of ACDE in RAW264.7 macrophages. ACDE significantly induced heme oxygenase-1 (HO-1) gene expression in RAW264.7 cells, while ACDE improved LPS-induced toxicity of cells. And ACDE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Further study demonstrated that ACDE-induced expression of HO-1 was inhibited by inhibitors of phosphatidylinositol 3-kinase (PI-3K) (LY294002), c-Jun kinase (JNK) (SP600125), extracellular signal regulated kinase (ERK) (PD98059) and p38 kinase (SB203580). Moreover, ACDE phosphorylated Akt, JNK, ERK, and p38 MAPK. In addition, ACDE inhibited LPS-induced NO secretion as well as inducible NO synthase (iNOS) expression in a dose-dependent manner. The inhibitory effects of ACDE on iNOS expression were abrogated by small interfering RNA (siRNA)-mediated knock-down of HO-1. Therefore, these results suggest that ACDE suppresses the production of pro-inflammatory mediator such as NO by inducing HO-1 expression via PI-3K/Akt/MAPK-Nrf2 signaling pathway. These findings could help us to understand the active principle included in the roots of A. japonica and the molecular mechanisms underlying anti-inflammatory action of ACDE.

Gardenia jasminoides Exerts Anti-inflammatory Activity via Akt and p38-dependent Heme Oxygenase-1 Upregulation in Microglial Cells (소교세포에서 heme oxygenase-1 발현 유도를 통한 치자(Gardenia jasminoides)의 항염증 효과)

  • Song, Ji Su;Shin, Ji Eun;Kim, Ji-Hee;Kim, YoungHee
    • Journal of Life Science
    • /
    • v.27 no.1
    • /
    • pp.8-14
    • /
    • 2017
  • Died Gardenia jasminoides fruit is used as a dye in the food and clothes industries in Asia. The present study investigated the anti-inflammatory effects of aqueous extract of G. jasminoides fruits (GJ) in BV-2 microglial cells. GJ inhibited lipopolysaccharide-induced nitric oxide (NO) secretion, inducible nitric oxide synthase (iNOS) expression, and reactive oxygen species production, without affecting cell viability. Furthermore, GJ increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner. Moreover, the inhibitory effect of GJ on iNOS expression was abrogated by small interfering RNA-mediated knock-down of HO-1. In addition, GJ induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. GJ-mediated expression of HO-1 was suppressed by LY294002, a phosphoinositide 3-kinase (PI-3K) inhibitor, and SB203580, a p38 kinase inhibitor, but not by the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or c-Jun N-terminal kinase (JNK) inhibitor SP600125. GJ also enhanced the phosphorylation of Akt and p38. These results suggest that GJ suppresses the production of NO, a pro-inflammatory mediator, by inducing HO-1 expression via PI-3K/Akt/p38 signaling. These findings illustrate a novel molecular mechanism by which extract from G. jasminoides fruits inhibits neuroinflammation.

Evaluation of Therapeutic Effect of the Extract from Rhubarb (Rheum officinalis) in Dogs with Chronic Renal Failure (개의 만성 신부전에서 대황 추출물의 치료학적 효과의 평가)

  • Kim, Ye-Won;Hyun, Changbaig
    • Journal of Veterinary Clinics
    • /
    • v.29 no.6
    • /
    • pp.435-440
    • /
    • 2012
  • This study was designed to evaluate the clinical efficacy and safety of Rhubarb extracts (Rubenal(R)) in dogs with chronic renal failure (CRF). Client-owned 40 dogs with CRF graded International renal interest Society (IRIS) II-III were enrolled in this study. The dogs were equally allocated and blindly administered with Rubenal(R) or placebo. The following items were evaluated at day 0, 30, 90 and 180: body condition score (BCS), clinical score (appetite, polydipsia/polyuria, quality of life score), hemogram (WBC, RBC, PCV), serum biochemistry (ALT/AST, ALP, Creatinine/BUN, total protein, albumin), serum electrolyte (Na, K, Cl, Ca, P), systolic blood pressure, urinalysis (UPC, USG) and IRIS stage. In this study, we found that the Rubenal(R) preparation was well tolerated by dogs and induced no adverse effects. Statistically significant improvements were observed in clinical score (quality of life score by vet and clients), serum BUN and creatinine levels, serum phosphorus concentration, level of proteinuria, and the IRIS score of CRF in dogs after 6 month of treatment of Rubenal(R). Those findings suggested that the Rhubarb extracts can improve the clinical signs of CRF (i.e. azotemia, hypertension, proteinuria, hyperphosphoremia) and the quality of life (i.e. BCS, clinical score) and can retard the progression of CRF in dogs. Therefore the Rhubarb extracts can be a good supplementary drug for treating dogs with subclinical and clinical renal diseases. However, care should be taken for interpreting our result, because this study is not double-blinded controlled study but pilot study.